Diana Bautista
Associate Professor of Cell and Developmental Biology
Department of Molecular and Cell Biology
University of California, Berkeley
(November 10, 2015)
Itchy and Scratchy: Molecular Mechanisms of Acute and Chronic Itch
Is there anything more annoying than an itch in a place you can’t quite reach? But why do we itch? At times it is beneficial, such as when it is a cue to swat away the mosquito before it gets much of a bite. But in some, the itch becomes chronic, for uncertain reasons. Dr. Bautista and her lab are working to identify the processes that underlie chronic itch, the first step in determining new treatments or cures. Her work in mice genetically modified to have chronic itch has found a first candidate, a serotonin receptor, which could be a target for future treatments.
Humans rely on the sensations of itch, touch, and pain for a broad range of essential behaviors. For example, acute pain acts as a warning signal that alerts us to noxious mechanical, chemical, and thermal stimuli, which are potentially tissue damaging. Likewise, itch sensations trigger reflexes that may protect us from disease-carrying insects. In addition, during inflammation or injury, we experience a heightened sensitivity to touch that encourages us to protect the injured site. Despite these essential protective functions, itch and pain can outlast their usefulness and become chronic. In mammals, these sensations are mediated by specialized subsets of somatosensory neurons that innervate the skin and viscera. Non-excitable cells, such as keratinocytes and immune cells, also work in conjunction with somatosensory neurons to promote and maintain acute and chronic inflammatory pain and itch. My lab aims to identify the mechanisms by which these cell types detect itch and tactile stimuli, under normal and pathophysiological conditions. We use a combination of cellular physiology, molecular biology, molecular genetics, and behavioral studies to probe the cellular and molecular mechanisms that mediate itch, touch, and pain. We recently examined the natural variation across genetically distinct mouse strains to identify transcripts co-regulated with itch behavior. This survey led to the discovery of a plethora of candidate itch transducers in skin, sensory neurons, and immune cells. We have shown that one such candidate, the serotonin receptor HTR7, is a key mediator of acute and chronic itch. Abberant serotonin signaling has long been linked to a variety of human chronic itch conditions, including atopic dermatitis. But the serotonin receptor subtypes that mediate chronic itch remained enigmatic. In a mouse model of atopic dermatitis, we have now shown that mice lacking HTR7 displayed significantly reduced itch-evoked scratching, inflammation, and skin lesion severity. These data highlight a role for HTR7 in acute and chronic itch, and suggest that HTR7 antagonists may be useful for treating a variety of pathological itch conditions.